title: Inhibiting toxic aggregation of amyloidogenic proteins: a therapeutic strategy for protein misfolding diseases.
abstract: BACKGROUND
  The deposition of self-assembled amyloidogenic proteins is associated with multiple diseases, including Alzheimer's disease, Parkinson's disease and type 2 diabetes mellitus. The toxic misfolding and self-assembling of amyloidogenic proteins are believed to underlie protein misfolding diseases. Novel drug candidates targeting self-assembled amyloidogenic proteins represent a potential therapeutic approach for protein misfolding diseases.
  
  
  METHODS
  In this perspective review, we provide an overview of the recent progress in identifying inhibitors that block the aggregation of amyloidogenic proteins and the clinical applications thereof.
  
  
  CONCLUSIONS
  Compounds such as polyphenols, certain short peptides, and monomer- or oligomer-specific antibodies, can interfere with the self-assembly of amyloidogenic proteins, prevent the formation of oligomers, amyloid fibrils and the consequent cytotoxicity.
  
  
  CONCLUSIONS
  Some inhibitors have been tested in clinical trials for treating protein misfolding diseases. Inhibitors that target the aggregation of amyloidogenic proteins bring new hope to therapy for protein misfolding diseases.
authors.affiliation: Tongji School of Pharmacy, Huazhong University of Science and Technology, Wuhan, People's Republic of China.
authors.forename: Biao
authors.initials: B
authors.lastname: Cheng
authors.forename: Hao
authors.initials: H
authors.lastname: Gong
authors.forename: Hongwen
authors.initials: H
authors.lastname: Xiao
authors.forename: Robert B
authors.initials: RB
authors.lastname: Petersen
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: Kun
authors.initials: K
authors.lastname: Huang
mesh_terms: D058227:Amyloidogenic Proteins / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D018384:Oxidative Stress; D017510:Protein Folding; D057165:Proteostasis Deficiencies / Q000378:metabolism*
chemical_list: D058227:Amyloidogenic Proteins
keywords: (−)-epigallocatechin 3-gallate; AChE; AD; AIF; Alzheimer's disease; Amyloid; Aβ; BBB; C/EBP Homologous Protein; CA; CD; CGA; CHOP; CNS; Cytotoxicity; EGCG; ER; FAP; HD; Htt; Huntington disease; Inhibitor; PD; PICUP; PMDs; Parkinson's disease; Polyphenols; Protein misfolding disease; ROS; SAR; T2DM; acetylcholinesterase; amyloid-beta; apoptosis induce factor; blood brain barrier; caffeic acid; central nervous system; chlorogenic acid; circular dichroism; endoplasmic reticulum; familial amyloid polyneuropathy; huntingtin; photo-induced cross-linking of unmodified proteins; protein misfolding diseases; reactive oxygen species; structure–activity relationships; type 2 diabetes mellitus